Obesity alters adipose tissue macrophage iron content and tissue iron distribution.
Obesity alters adipose tissue macrophage iron content and tissue iron distribution.
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作者：
Orr JS;Kennedy A;Anderson-Baucum EK;Webb CD;Fordahl SC;Erikson KM;Zhang Y;Etzerodt A;Moestrup SK;Hasty AH
脂肪组织 (AT) 扩张伴随着 AT 巨噬细胞 (ATM) 的浸润和积累，以及 ATM 极化的转变。多项研究表明，M1 ATM 的募集与肥胖的代谢后果有关。然而，关于替代激活的常驻 M2 ATM 在 AT 稳态中的作用或它们的功能在肥胖中如何改变，人们知之甚少。在此，我们报告了一组替代激活的 ATM 的发现，这些 ATM 具有升高的细胞铁含量和铁回收基因表达谱。这些富含铁的 ATM 称为 MFehi，其余 ATM 称为 MFelo。在瘦小鼠中，约 25% 的 ATM 是 MFehi；由于 MFelo 巨噬细胞的募集，肥胖率下降。与 MFelo 细胞类似，MFehi ATM 在肥胖症中也会发生炎症转变。在体内，肥胖会降低 MFehi ATM 的铁含量以及铁输入者和铁输出者铁转运蛋白的基因表达，表明处理铁的能力受损。在体外，初级腹膜巨噬细胞暴露于饱和脂肪酸也会改变铁代谢基因的表达。最后，MFehi 铁处理受损与肥胖小鼠的脂肪细胞铁超载相一致。总之，在肥胖症中，铁的分布在细胞和组织水平上都发生了改变，而 AT 在这种变化中发挥着主导作用。肥胖期间脂肪酸可用性的增加可能导致观察到的 MFehi ATM 表型变化及其处理铁的能力降低。
Adipose tissue (AT) expansion is accompanied by the infiltration and accumulation of AT macrophages (ATMs), as well as a shift in ATM polarization. Several studies have implicated recruited M1 ATMs in the metabolic consequences of obesity; however, little is known regarding the role of alternatively activated resident M2 ATMs in AT homeostasis or how their function is altered in obesity. Herein, we report the discovery of a population of alternatively activated ATMs with elevated cellular iron content and an iron-recycling gene expression profile. These iron-rich ATMs are referred to as MFehi, and the remaining ATMs are referred to as MFelo. In lean mice, ~25% of the ATMs are MFehi; this percentage decreases in obesity owing to the recruitment of MFelo macrophages. Similar to MFelo cells, MFehi ATMs undergo an inflammatory shift in obesity. In vivo, obesity reduces the iron content of MFehi ATMs and the gene expression of iron importers as well as the iron exporter, ferroportin, suggesting an impaired ability to handle iron. In vitro, exposure of primary peritoneal macrophages to saturated fatty acids also alters iron metabolism gene expression. Finally, the impaired MFehi iron handling coincides with adipocyte iron overload in obese mice. In conclusion, in obesity, iron distribution is altered both at the cellular and tissue levels, with AT playing a predominant role in this change. An increased availability of fatty acids during obesity may contribute to the observed changes in MFehi ATM phenotype and their reduced capacity to handle iron.
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